Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.
Genome-wide association studies of smooth pursuit and antisaccade eye movements in psychotic disorders: findings from the B-SNIP study.
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DOI：
10.1038/tp.2017.210
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发表时间：
2017-10-24
影响因子：
6.8
通讯作者：
Bishop JR
中科院分区：
文献类型：
--
作者：
Lencer R;Mills LJ;Alliey-Rodriguez N;Shafee R;Lee AM;Reilly JL;Sprenger A;McDowell JE;McCarroll SA;Keshavan MS;Pearlson GD;Tamminga CA;Clementz BA;Gershon ES;Sweeney JA;Bishop JR
眼动偏差，特别是初始感觉运动加工和持续追求维持的缺陷，以及抗眼跳抑制错误，是精神病的中间表型。本研究研究了来自双相-精神分裂症中间表型网络（B-SNIP）研究的849名参与者（精神分裂症N=230，分裂情感性障碍N=155，精神病性双相障碍N=206和健康对照N=258）的眼动测量作为与遗传数据相关的定量表型，同时控制了遗传来源的祖先测量、年龄和性别。采用混合建模全基因组关联研究方法，包括约440万个基因型（PsychChip和1000个基因组植入）。在所有参与者中，追求开始时的感觉运动加工与IPO8的单核苷酸多态性显著相关（12p11.21， P=8 × 10−11），而与持续追求维持的暗示关联则与SH3GL2的snp有关（9p22.2， P=3 × 10−8）。在主要为非洲血统的参与者中，感觉运动加工也与PCDH12中的snp显著相关（5q31.3， P=1.6 × 10−10），并且与NRSN1 （6p22.3， P=5.4 × 10−8）和LMO7 （13q22.2， P=7.3 × 10−8）存在暗示关联，而抗扫视错误率与7号染色体上的非编码区显著相关（P=6.5 × 10−9）。探索性通路分析显示，40个顶级基因与感觉运动加工和追求维持有关，与神经系统发育和功能有关（P=4.9 × 10−2-9.8 × 10−4）。我们的发现提示了一种新的遗传变异模式，这种模式与精神疾病中已知的眼动控制受损的大脑系统有关。它们包括参与核运输和基因沉默（IPO8）、快速轴突引导和突触特异性（PCDH12）、神经信号转导（NRSN1）、视网膜变性（LMO7）、突触谷氨酸释放（SH3GL2）以及更广泛的神经系统发育和功能的基因。
Eye movement deviations, particularly deficits of initial sensorimotor processing and sustained pursuit maintenance, and antisaccade inhibition errors, are established intermediate phenotypes for psychotic disorders. We here studied eye movement measures of 849 participants from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study (schizophrenia N=230, schizoaffective disorder N=155, psychotic bipolar disorder N=206 and healthy controls N=258) as quantitative phenotypes in relation to genetic data, while controlling for genetically derived ancestry measures, age and sex. A mixed-modeling genome-wide association studies approach was used including ~4.4 million genotypes (PsychChip and 1000 Genomes imputation). Across participants, sensorimotor processing at pursuit initiation was significantly associated with a single nucleotide polymorphism in IPO8 (12p11.21, P=8 × 10−11), whereas suggestive associations with sustained pursuit maintenance were identified with SNPs in SH3GL2 (9p22.2, P=3 × 10−8). In participants of predominantly African ancestry, sensorimotor processing was also significantly associated with SNPs in PCDH12 (5q31.3, P=1.6 × 10−10), and suggestive associations were observed with NRSN1 (6p22.3, P=5.4 × 10−8) and LMO7 (13q22.2, P=7.3x10−8), whereas antisaccade error rate was significantly associated with a non-coding region at chromosome 7 (P=6.5 × 10−9). Exploratory pathway analyses revealed associations with nervous system development and function for 40 top genes with sensorimotor processing and pursuit maintenance (P=4.9 × 10−2–9.8 × 10−4). Our findings suggest novel patterns of genetic variation relevant for brain systems subserving eye movement control known to be impaired in psychotic disorders. They include genes involved in nuclear trafficking and gene silencing (IPO8), fast axonal guidance and synaptic specificity (PCDH12), transduction of nerve signals (NRSN1), retinal degeneration (LMO7), synaptic glutamate release (SH3GL2), and broader nervous system development and function.
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DOI：
10.1176/appi.ajp.2015.14091200
发表时间：
2016-04-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Clementz BA;Sweeney JA;Hamm JP;Ivleva EI;Ethridge LE;Pearlson GD;Keshavan MS;Tamminga CA
通讯作者：
Tamminga CA
影响因子：
3.7
作者：
Forstner AJ;Hecker J;Hofmann A;Maaser A;Reinbold CS;Mühleisen TW;Leber M;Strohmaier J;Degenhardt F;Treutlein J;Mattheisen M;Schumacher J;Streit F;Meier S;Herms S;Hoffmann P;Lacour A;Witt SH;Reif A;Müller-Myhsok B;Lucae S;Maier W;Schwarz M;Vedder H;Kammerer-Ciernioch J;Pfennig A;Bauer M;Hautzinger M;Moebus S;Schenk LM;Fischer SB;Sivalingam S;Czerski PM;Hauser J;Lissowska J;Szeszenia-Dabrowska N;Brennan P;McKay JD;Wright A;Mitchell PB;Fullerton JM;Schofield PR;Montgomery GW;Medland SE;Gordon SD;Martin NG;Krasnov V;Chuchalin A;Babadjanova G;Pantelejeva G;Abramova LI;Tiganov AS;Polonikov A;Khusnutdinova E;Alda M;Cruceanu C;Rouleau GA;Turecki G;Laprise C;Rivas F;Mayoral F;Kogevinas M;Grigoroiu-Serbanescu M;Becker T;Schulze TG;Rietschel M;Cichon S;Fier H;Nöthen MM
通讯作者：
Nöthen MM
影响因子：
4.4
作者：
Giachino, C;Lantelme, E;Migone, N
通讯作者：
Migone, N
影响因子：
3.7
作者：
CLEMENTZ, BA;SWEENEY, JA;HAAS, G
通讯作者：
HAAS, G
影响因子：
17.7
作者：
Ettinger, U;Kumari, V;Sharma, T
通讯作者：
Sharma, T